The object of the proposed investigation is to gain additional insights into the molecular events and regulatory mechanisms in the alteration of cell structure and function during the mammalian cell cycle. Synchronized HeLa S3 cells and adenovirus type 2 transformed cell lines will be employed for these investigations. Alterations in the structure and function of the nuclear matrix in the cell cycle will be investigated by asking specific questions concerning the synthesis, fate and structural relationships of the polypeptide components. The feasibility of studying the breakdown and reassembly of the matrix at the time of mitosis will be evaluated by an attempt to construct three dimensional models of the structure from electron micrographs. The activity of Mg ions dependent adenosine triphosphatase (MgATPase) and the synthesis of fragments of adenovirus DNA associated with this structure will be used to explore the functional significance of this subnuclear structure. Details of the biochemical mechanisms involved in the regulation of gene expression during the cell cycle will be investigated by a study of the synthesis of the virus-specific RNA in adenovirus 2 transformed rat embryo cells. The relationship between the control of the expression of the integrated viral genome and the cellular genome will be studied in synchronized cells, and should increase our knowledge of the independence and dependence of the transforming viral genome on cellular functions. BIBLIOGRAPHIC REFERENCE: Nuclear and cytoplasmic adenovirus RNA: Differences between 5'-termini of messenger and non-messenger transcripts. McGuire, P.M., Piatak, M. and L.D. Hodge. J. Mol. Biol. 101, in press (1976).